1. Field of the Invention
The present invention is in the field of arthritis and pharmacotherapy of arthritis and joint diseases. More specifically, the present invention is directed to novel peptides which home to joints and uses thereof.
2. Description of the Related Art
Rheumatoid arthritis (RA) is a T-cell-mediated autoimmune disease (1). Both the joint-resident and systemic antigens have been invoked in the pathogenesis of RA (2, 3). Furthermore, the joints are frequently targeted in pathological conditions associated with systemic autoimmunity (4). A major challenge in this regard lies in defining the mechanisms underlying the selective targeting of the joints in the face of systemic autoimmunity. The migration of pathogenic T cells and other leukocytes into the joints depends on the interaction between the leukocytes and the target organ vasculature. In addition, angiogenesis plays am important role in the disease process in RA (5, 6). Thus, targeting the blood vessels is of major interest for developing novel therapeutic interventions in this disease (5-8).
The vascular bed of individual tissues is highly specialized, with endothelial cells expressing unique molecules (9, 10). Furthermore, during the process of angiogenesis, the new blood vessels express many cell surface molecules not found in normal blood vessels. The use of in vivo screening of phage peptide display libraries has been instrumental in identifying tissue/organ-specific and disease-specific vascular markers (9, 11-13). The molecular differences in the vascular endothelium of various tissues/organs have been termed as “molecular addresses” or “zip codes” (9-11). For example, a nonapeptide was found to home to normal breast tissue and to bind to aminopeptidase P in breast vasculature (14). Similarly, peptides homing specifically to brain, kidney, lung, heart, skin, pancreas, retina, and prostate have been identified (9). In all of these tissues, the phage was localized in the blood vessels. The main target of phage-encoded peptide ligands has been the tumors (15-19); the vasculature of the inflamed joint has not been probed in that manner.
The prior art is deficient in novel peptides that home to joints as well as methods of their use. The present invention fulfills this longstanding need and desire in the art.